Antigenic variation was observed in the expression of specific tumor-associated antigens within individual human mammary tumor masses using monoclonal antibodies. This variation was demonstrated by both the pattern and cellular localization of reactivity with a given antibody. This diversity was also observed in human mammary tumor cell lines grown in vivo and in vitro. Analyses of DNA content and cell surface binding of monoclonal antibodies during logarithmic growth phase, and at density-dependent arrest, demonstrated that the expression of some tumor-associated antigens is related to S-phase of the cell cycle. Membrane expression of the reactive antigens appeared to be stable despite prolonged exposure to antibody. Antigenic drift was observed with continued passage of mammary tumor cell lines; consistent with this finding, the "same" mammary tumor cell line obtained from different sources exhibited distinct antigenic phenotypes. Preliminary results indicate that exposure of mammary tumor cells to certain compounds may enhance the cell surface expression of some tumor-associated antigens.